Is BRD4 p.Asp231Ala (c.692A>C) pathogenic?

BRD4 p.Asp231Ala (c.692A>C) is classified Uncertain significance in BRD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-29). AlphaMissense: ambiguous (0.3497); Ultra-rare (popmax 0.0424%, eas); Associated with Inborn genetic diseases.

What condition is associated with BRD4 p.Asp231Ala (c.692A>C)?

BRD4 p.Asp231Ala (c.692A>C) is associated with Inborn genetic diseases (ClinVar).

How common is BRD4 p.Asp231Ala (c.692A>C) in the general population?

BRD4 p.Asp231Ala (c.692A>C) is ultra-rare (popmax 0.0424%, eas) (gnomAD).

What do computational predictors say about BRD4 p.Asp231Ala (c.692A>C)?

AlphaMissense predicts ambiguous (score 0.3497) — an in-silico prediction, not a clinical call.

BRD4 p.Asp231Ala

c.692A>C · rs199801990 · VCV2386904

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3497 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0424%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3497	ambiguous
REVEL	0.143	moderately benign-leaning
SaProt	LLR -3.36	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 279 bp · p 0.47 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0424% East Asian · 19/44,826 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00118% 19/1,612,424 alleles · ultra-rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: BRD4
Protein: p.Asp231Ala
Coding: c.692A>C
MANE Select: NM_001379291
dbSNP: rs199801990
Type: single nucleotide variant
Location: chr19:15265511 (GRCh38)
Gene constraint: LOEUF 0.191 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.20 · 613 PDB

Full BRD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BRD4 p.Asp231Asn Uncertain significance ★ ⚠ same residue
BRD4 p.Asp231Glu Uncertain significance ★ ⚠ same residue
BRD4 p.Ala220Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala409Thr Uncertain significance ★★ ⚠ same condition
BRD4 p.Ala565Val Uncertain significance ★★ ⚠ same condition
BRD4 p.Asp497Gly Uncertain significance ★★ ⚠ same condition
BRD4 p.Gln32Arg Uncertain significance ★★ ⚠ same condition
BRD4 p.Glu715Lys Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/brd4-p-asp231ala (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown